Currently, the abuse of heroin and prescription opioid medications is a pervasive social problem in the U.S. Similarly, the prevalence of tobacco use among adults in the U.S. is approximately 20%, despite intensive efforts to reduce its use. We are proposing to test the ability of pioglitazone, a peroxisome proliferator-activated receptor- gamma (PPAR) agonist that is FDA-approved for use in the management of type 2 diabetes mellitus, to reduce abuse of heroin (Study 1), and cigarette smoking (Study 2). Pioglitazone will be tested in combination with buprenorphine/naloxone (Study 1) and with the nicotine patch (Study 2). These studies were based on a series of unpublished preclinical data showing that pioglitazone may have utility in treating opioid and nicotine dependence. Participants in all studies will live on a locked inpatient unit and will be tested in the laboratory. The ability of pioglitazone to alter drug self-administration, reactivity to drug cues, and relapse to drug use will be assessed. In addition, subjective responses, such as ratings of drug liking, craving, and desire to take the drug again will be evaluated. Potential toxicity of the medication combinations will be assessed by measuring cognitive performance and physiological responses. The results of these studies will provide a great deal of information about the effects of pioglitazone in combination with agonist replacement therapies. If the results of the proposed studies support the preclinical data with pioglitazone, they may reveal a previously unidentified target for medications development for substance abuse.

Public Health Relevance

Heroin and prescription opioid abuse are prevalent in the U.S., as is cigarette smoking. The purpose of the present proposal is to characterize the ability of pioglitazone, a medication currently used to treat diabetes, to alter the abuse liability of heroin (Study 1) and of cigarette smoking (Study 2). Pioglitazone will be given in combination with buprenorphine/naloxone (Study 1) or the nicotine patch (Study 2).

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA031022-04
Application #
8487385
Study Section
Special Emphasis Panel (ZDA1-JXR-D (10))
Program Officer
Hampson, Aidan
Project Start
2010-09-30
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$833,527
Indirect Cost
$166,396
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M et al. (2016) The effects of pioglitazone, a PPARγ receptor agonist, on the abuse liability of oxycodone among nondependent opioid users. Physiol Behav 159:33-9
Jones, Jermaine D; Vadhan, Nehal P; Luba, Rachel R et al. (2016) The effects of heroin administration and drug cues on impulsivity. J Clin Exp Neuropsychol 38:709-20
Askalsky, Paula; Kalapatapu, Raj K; Foltin, Richard W et al. (2015) Butyrylcholinesterase levels and subjective effects of smoked cocaine in healthy cocaine users. Am J Drug Alcohol Abuse 41:161-5
Vosburg, Suzanne K; Jones, Jermaine D; Manubay, Jeanne M et al. (2013) A comparison among tapentadol tamper-resistant formulations (TRF) and OxyContin® (non-TRF) in prescription opioid abusers. Addiction 108:1095-106
Jones, Jermaine D; Comer, Sandra D (2013) A review of human drug self-administration procedures. Behav Pharmacol 24:384-95
Gudin, Jeffrey A; Mogali, Shanthi; Jones, Jermaine D et al. (2013) Risks, management, and monitoring of combination opioid, benzodiazepines, and/or alcohol use. Postgrad Med 125:115-30
Smith, Shannon M; Dart, Richard C; Katz, Nathaniel P et al. (2013) Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations. Pain 154:2287-96
Turk, Dennis C; O'Connor, Alec B; Dworkin, Robert H et al. (2012) Research design considerations for clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations. Pain 153:1997-2008
Vosburg, Suzanne K; Jones, Jermaine D; Manubay, Jeanne M et al. (2012) Assessment of a formulation designed to be crush-resistant in prescription opioid abusers. Drug Alcohol Depend 126:206-15
Jones, Jermaine D; Mogali, Shanthi; Comer, Sandra D (2012) Polydrug abuse: a review of opioid and benzodiazepine combination use. Drug Alcohol Depend 125:8-18

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